Continued support is sought for a multifaceted study of human and experimental muscle diseases with light, phase and electron microscopy, electron microscopic cytochemistry, immunoelectron microscopy, tissue culture methods, freeze-fracture electron microscopy and correlative biochemical and electrophysiological investigations. Ultrasturctural reactions of muscle fibers organelles and of the neuromuscular junction will beinvestigatedand quantitated by morphometric method. Myasthenia gravis and its autoimmune model will be analyzed to establish the relative importance of immunopathologic mechanisms which result in deficiency of the acetylcholine receptor (AChR). The ultrastructural aspects of modulation of AChR by antibody and the role of the complement membzane attack components in the pathogenesis of the destructive changes at the end-plate will be investigated. In the Lambert-Eaton myasthenic syndrome a search will be made for a presynaptic morphologic correlate of the impaired neuromuscular transmission. In a newly recognized, congenital, familial myasthenic syndrome attributed to a presyanptic defect fo acetylcholine resynthesis, biochemical and ultrastructural studies will be done to elucidate the pathogenesis. In another newly recognized and genetically determined myasthenic syndrome attributed to molecular abnormality of AChR, ultrastructural and biochemical studies will be done to reveal the cause of the muscle weakness. In Duchenne dystrophy the plasma membrane of the cultures muscle will be investigated by freeze-fracture electron microscopy. In carnitine deficiency cultured muscle cells will be studied for a postulated abnormality of carnitine transport. The biochemical basis of an adult onset polyglucosan storage disease will be investigated.